The bacterial regulatory protein H-NS--a versatile modulator of nucleic acid structures.

The small DNA binding protein H-NS is attracting broad interest for its profound involvement in the regulation of bacterial physiology. It is involved in the regulation of many genes in response to a changing environment and functions in the adaptation to many different kinds of stress. Many H-NS-controlled genes, including the hns gene itself, are further linked to global regulatory networks. H-NS thus plays a key role in maintaining bacterial homeostasis under conditions of a rapidly changing environment. In this review we summarize recent results from combined biochemical and biophysical efforts which have yielded new insights into the three-dimensional structure and function of H-NS. The protein consists of two distinct domains separated by an unstructured linker region, and the structural details available today have helped to understand how these domains may interact with each other or with ligand molecules. Functional studies have, in addition, revealed mechanistic clues for the various H-NS activities, like temperature- or growth phase-dependent regulation. Important elements for the specific regulatory activities of H-NS comprise different modes of DNA binding, protein oligomerization, the competition with other regulators and the fact that the topology of the target DNA is modulated during complex formation. The distinctive ability to recognize nucleic acid structures in combination with other proteins also explains H-NS-dependent post-transcriptional activities where the interaction with defined RNA structures and the interference with RNA/protein complexes during mRNA translation are crucial for regulation. Thus, protein/protein interactions, in combination with the recognition and modulation of nucleic acid structures, are key elements of the different mechanisms which make H-NS such a versatile regulator.